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Some Cancer Patients May Benefit From a Less Aggressive Approach to Stem Cell Transplant Therapy

WASHINGTON, December 3, 2001 — Conventional wisdom over the past 30 years has developed a well-defined path for physicians who recommend stem cell transplants for their cancer patients – destroy the blood cell factory and the immune system completely before you can rebuild it. But to paraphrase George Gershwin, new research indicates it ain’t necessarily so.

“In the past, this so-called ‘conditioning regimen’ has involved high doses of cancer chemotherapy drugs, sometimes in combination with radiation treatments to the entire body,” said Andrew Yeager, M.D., a professor of medicine and pediatrics at the University of Pittsburgh School of Medicine. “This intensive treatment was effective in getting rid of the patient’s blood cells and immune responses, but had its own toxicities to normal vital organs and tissues. The transplant patient’s damaged cells set off a storm of cytokines – proteins that cause inflammation – which in turn caused more transplant-related complications.”

New research is beginning to indicate that cell transplantation without such aggressive conditioning regimens can still be effective in treating certain cancers, continued the physician, who is also director of stem cell transplantation at the University of Pittsburgh Cancer Institute.

Dr. Yeager made a presentation, “Is Less Really More? An Update on Nonmyeloablative Hematopoietic Cell Transplantation,” at the Second Annual Conference on Regenerative Medicine, a gathering of clinicians and other specialists in the fields of stem cell research, medicine and biotechnology that ends Tuesday at the Renaissance Washington, D.C. Hotel.

Hematopoietic cells are progenitor cells found in adult bone marrow and, to a lesser extent, in the peripheral bloodstream. Researchers believe these cells, also known as CD34-positive cells, can become blood cells and immune system cells.

“They can be used to build a new blood-cell factory,” said Dr. Yeager, who was featured in a CBS 60 Minutes II report on stem cell transplantation for sickle cell anemia on Nov. 28. “But the key question is, can the graft survive? The goal is to get these cells in so the patient doesn’t reject them.”

Using a less destructive conditioning regimen may be a viable option, said Dr. Yeager.

“Experiments using a mouse model have shown that you can get a low level of stem cell growth from transplant without doing anything to damage the native immune system,” he added. “And other studies have found that there still is a lot of growth with just immunosuppression that doesn’t destroy the bone marrow first.”

Thus far, stem cell transplant therapies with less intensive conditioning treatments seem most effective for cancers such as leukemia and lymphoma and a cancer of the kidney called renal cell carcinoma. Because of many subtle differences between cancers, however, it is difficult to determine a single treatment option, or even a single way of carrying out a treatment.

“We need to refine the regimens,” said Dr. Yeager. “Over time, the hope is to increase donor cells that rebuild healthy blood cells and get rid of cancer cells in the recipient without causing the acute problems that can happen after regular full-dose transplants.”

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